Targeted and controlled drug delivery system loading artersunate for effective chemotherapy on CD44 overexpressing cancer cells

Abstract

Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with negative surface charge were reversed to positive by cationic surfactant-DDAB before being coated with an anionic polymer, hyaluronic acid, to improve their site-specific intracellular delivery against CD44 receptor overexpressing cancer cells. Incorporating artesunate (ART)-a promising anticancer drug into PLGA/HA nanoparticles, is expected not only to overcome its poor aqueous solubility and stability but also enhance the activities. The obtained particles were characterized by dynamic light scattering, zeta potential measurements, and transmission electron microscopy (TEM). Cancer cell internalization of the NPs was evaluated by flow cytometry and cytotoxicity of the NPs was tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. PLGA/HA nanoparticles showed greater extent of cellular uptake to SCC-7 and MCF-7 cells, indicating their affinity with CD44 receptor-mediated endocytosis. Almost 60 % of ART was released into the outer media after 48 h. In vitro fluorescence sorting demonstrated that PLGA/HA had highly efficient targeting and accumulation into CD44 receptor overexpression cells. The significant reduction in cell viability as well as greater induction of apoptosis suggested a potential in anticancer therapy of ART loaded PLGA/HA.

Progress in nano-drug delivery of artemisinin and its derivatives: towards to use in immunomodulatory approaches

“…It was observed suitable immunomodulation of the drug with high delayedtype hypersensitivity (DTH) response, increase of INF-c and IL-2 and reduction of IL-4 and IL-10 indicating Th1 immune response pattern resulting in clearance of the parasite [27]. Other studies conducted with PLGA NPs and other ART derivatives revealed high cytotoxicity in SCC-7, MCF-7 and HepG2 cell lines with growth inhibition and induced apoptosis, compared with free drugs [28,29].…”

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

“…The formulation was diluted by distilled water prior to three replicate measurements. After negative staining dispersion with 2 % (w/v) phosphotungstic acid, nanoparticles were placed into copper grid and observed by TEM (H7600, Hitachi, Tokyo, Japan) [24] .…”

A Promising Biocompatible Platform: Lipid-Based and Bio-Inspired Smart Drug Delivery Systems for Cancer Therapy

“…Hyaluronic acid (HA) is a molecule with targeting specificity for the CD44 receptor. This linear glycosaminoglycan can bind to the surface of CD44-overexpressing cancers, which include cancers of the head and neck, as well as gastric, colon, prostate, hepatic and breast cancers [93,94]. However, the molecular weight of HA varies, which could affect cellular uptake [78]; thus, the efficacies of drug carriers might depend on the molecular weight of HA, which suggests that HA with an appropriate molecular weight will be selected for specific targets [95,96].…”